(Stroke. 1995;26:1409-1414.)
© 1995 American Heart Association, Inc.
Articles |
Cigarette Smoking Accelerates Carotid Artery Intimal Hyperplasia in a Dose-Dependent Manner
Presented at the 20th International Joint Conference on Stroke and Cerebral Circulation, Charleston, SC, February 9-11, 1995.
From the Section of Vascular Surgery, University of California at Los Angeles School of Medicine.
Correspondence to Hugh A. Gelabert, MD, UCLA School of Medicine, 10833 Le Conte Ave, Los Angeles, CA 90024.
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Abstract |
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Background and Purpose Intimal hyperplasia is the single most important cause of early restenosis after carotid endarterectomy. Cigarette smoking is an independent risk factor associated with peripheral vascular disease and cerebrovascular accidents. We undertook a dose-response experiment to determine the effect of cigarette smoke on development of intimal hyperplasia in a rat carotid artery intimal injury model.
Methods Seventy-two rats were divided into six equal groups and underwent standardized balloon injury to the carotid artery. Each group received 0 (controls), 1, 2, 3, 6, or 8 cigarettes per day for 4 weeks. Resultant intimal hyperplasia was expressed as a percentage of original lumen replaced by intimal hyperplasia.
Results Percent intimal hyperplasia development (±SD) was as follows: controls (0 cigarettes per day), 17.7±13.2; 1 cigarette per day, 22.8±15.0; 2 cigarettes per day, 20.0±14.7; 3 cigarettes per day, 19.2±12.1; 6 cigarettes per day, 43.5±15.5; and 8 cigarettes per day, 36.7±9.8. Six and 8 cigarettes per day significantly increased the development of intimal hyperplasia after intimal injury (P<.01).
Conclusions High-dose cigarette smoke accelerates development of intimal hyperplasia and may pose a significant risk factor in developing carotid restenosis.
Key Words: carotid arteries • cigarette smoking • hyperplasia • rats
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Stroke is the third leading cause of death in the United States and is associated with a high rate of morbidity.1 There are approximately 500 000 new stroke victims in the United States each year, and in 200 000 of these cases death quickly follows. At any one time, approximately one million stroke victims are alive and disabled.2 Carotid endarterectomy provides a means of restoring blood flow to affected cerebral areas and reduces the incidence of subsequent stroke.3 4 As the number of carotid endarterectomies performed in this country increases, so does the diversity of opinion regarding all elements of the operation. Proponents of carotid endarterectomy have sought to identify means of reducing both early and late surgical morbidity to improve surgical outcome.
Among the surgical complications targeted by these efforts is the problem of recurrent carotid stenosis. Restenosis rates of greater than 50% diameter reduction vary from 4% to 22%.5 6 7 8 9 10 11 12 13 Because of this, noninvasive monitoring of the carotid artery at regular intervals postoperatively, with surgery for stenosis greater than 80%, has been recommended.10 The majority of recurrent stenoses remain asymptomatic, and in most series symptoms are limited to severe lesions. The lack of data on the natural history of severe stenosis and on the risk factors for stenosis development preclude an informed decision on the role of surveillance or surgery.
Numerous risk factors have been investigated for an association with restenosis, including age,10 14 15 sex,6 11 13 15 16 17 diabetes,6 10 and smoking,6 15 16 17 18 each with varying results. Smoking in particular has demonstrated mixed results. We investigated the dose-response effect of cigarette smoke on the development of intimal hyperplasia in a well-described animal model.
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Materials and Methods |
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Seventy-two (six groups of 12 each) Sprague-Dawley rats weighing 300 to 500 g were placed in a smoking apparatus (detailed below) and exposed to increasing amounts of cigarette smoke daily until doses of 1, 2, 3, 6, and 8 cigarettes per day were achieved. Animals received their target smoke dosing for 1 week and then underwent standardized balloon injury of the carotid artery intima.
Our technique for standardized arterial balloon injury involves unilateral dissection of the right common carotid artery and cannulation of the external carotid artery. A 2F Fogarty balloon catheter (American Edwards Labs) was inserted and passed proximally toward the aortic arch. The balloon was inflated to 2 atm (Namic Co, Angiographic System Division) and withdrawn to the carotid artery bifurcation, resulting in denudation of the endothelium. The procedure was repeated three times with 120° rotation of the catheter between passes. This technique has been shown to induce a reproducible injury and has been used extensively in our laboratory.
The animals were exposed to cigarette smoke in an apparatus
designed at the University of Kentucky for small animal smoke
dosing.19 20 Rats were placed into individual wire
containers that restrained them such that only their snouts were
exposed in the intake port of the container. Eight rats restrained in
this manner were then placed onto the exhaust manifold of the smoke
machine at a time (Fig 1
). Puffing was simulated by
placing a lighted standard reference research cigarette (R1F4
cigarettes, University of Kentucky Tobacco and Health Research
Institute) into a holder and subjecting it to 1 second of vacuum at
1-minute intervals. Smoke was conducted to the exhaust port by means of
Tygon tubing (Norton Performance Plastics). Excess smoke was
evacuated from the exhaust manifold by a separate vacuum source. The
system was tuned such that 10 "puffs" fully consumed one
cigarette. Rats were allowed 10-minute rest periods between each
cigarette. The animals were exposed to their target dose of cigarette
smoke 5 days a week for 4 weeks.
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The vessels were then harvested by injection of 10 mL of 1% glutaraldehyde into the aortic root at systemic pressure to provide in vivo fixation while anatomic dimensions were maintained. After several minutes the animals were killed, and the arterial specimens were placed in 10% buffered formaldehyde. Three serial cross sections through the midportion of each artery were stained with Verhoeff–van Gieson stain by a professional histology laboratory (VCA Clinical Lab, Los Angeles, Calif).
The slide-mounted arterial lesions were studied with the
use of morphometric analysis to quantitate the size of the
intimal hyperplastic lesion. Photomicrographs of the stained sections
were taken at a power of x80. Using a digital desktop planimeter
(Lasico Graphic Digitizers) that converts tracings made by a hand-held
cursor into units of length and area, we calculated the absolute
cross-sectional area occupied by the intimal hyperplasia lesion and the
circumference of the internal elastic lamina (IEL). Using this
measurement of the IEL, we calculated the radius of the vessel by the
following mathematical formula: Circumference (IEL measurement)=2
r;
r=IEL/2. Substituting this value of r into the formula
r2 allows for calculation of a normalized luminal area.
The hyperplastic lesion was then expressed as a percentage of the
luminal area, allowing comparison among vessels of differing
caliber.
Animal care complied with the "Principles of Laboratory Animal Care" (formulated by the National Society for Medical Research) and the Guide for the Care and Use of Laboratory Animals (National Institutes of Health publication No. 86-23, revised 1985).
Statistical analysis of intimal hyperplasia percent differences between controls and smoke-exposure groups included ANOVA and Dunnett's comparison.
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Results |
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Four deaths occurred at the time of preinjury smoke exposure, and six animals died after initial arterial injury. These animals were replaced with similarly pretreated animals. During the 4-week course of postinjury smoking, the following deaths per group occurred: 4 controls, 1 one-cigarette-per-day animal, 3 two-cigarettes-per-day animals, 1 six-cigarettes-per-day animal, and 5 eight-cigarettes-per-day animals. Control animals and several smoking cohort deaths were secondary to carotid artery stripping as evidenced by listless behavior, poor appetite, and partial paralysis immediately after recovery from anesthesia. These animals failed to recover over a period of time and were killed. At the time of vessel harvesting, no wound infections or other surgical complications were noted.
The results of the planimetric intimal hyperplasia/IEL calculations are
summarized in the Table. An index of 0.00% indicates no
intimal hyperplasia; 100% would represent complete occlusion.
No statistical differences were shown in intimal hyperplasia percentage
ratios between controls and animals exposed to low-dose (1, 2, and 3
cigarettes per day) cigarette smoke (P>.05). Animals
receiving high doses of cigarette smoke (6 or 8 cigarettes per day) had
statistically increased intimal hyperplasia percentage ratios compared
with controls (P<.01).
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Fig 2 shows a control artery with a large amount of
intimal hyperplasia 4 weeks after a balloon catheter injury. Fig 3 shows an arterial cross section 4 weeks
after a similar balloon catheter endothelial denudation
and low-dose (1, 2, or 3 cigarettes per day) smoke exposure. The most
significant amounts of intimal hyperplasia were demonstrated in animals
exposed to high-dose (6 or more cigarettes per day) smoke for 4 weeks
after balloon catheter injury (Fig 4).
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Discussion |
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Recurrent arterial stenosis, first reported in the carotid artery by Stoney and String in 1976,21 had been recognized years earlier as contributing to vascular reconstructive failures.22 23 Numerous studies suggest that the majority of stenoses are fibroproliferative lesions of intimal hyperplasia that develop within 2 years of surgery and are asymptomatic when discovered.6 11 12 13 16 17 24 25 26 27 Studies following up patients after carotid endarterectomy with serial duplex ultrasound of the carotid artery demonstrate variable rates of restenosis; a greater than 50% diameter reduction was demonstrated in 4% to 22% of patients,5 6 7 8 9 10 11 12 13 and Park et al7 demonstrated 50% to 75% stenosis in 8.5% of patients and greater than 80% stenosis in 4% of patients followed up for a mean of 47 months after carotid endarterectomy. Although controversy exists as to the indications for reoperation, most clinicians currently recommend reoperation for symptomatic patients or those with greater than 80% stenosis.10
As a result of the frequency of restenosis after carotid endarterectomy and the morbidity associated with reoperation, many investigators have searched for risk factors associated with restenosis. Numerous patient-dependent characteristics have been investigated for association with an increased incidence of restenosis, including age,10 14 15 sex,6 11 13 15 16 17 diabetes,6 10 and smoking,6 15 16 17 18 each with varying results. Smoking, in particular, has demonstrated mixed results. Clagett et al15 and Reilly et al18 showed an increased incidence of restenosis in smokers, whereas Atnip et al,6 Ouriel and Green,17 and Thomas et al16 found no such relationship. We have demonstrated that exposure to high-dose cigarette smoke increases development of intimal hyperplasia in the injured carotid artery.
Previous clinical studies on the relationship between smoking and restenosis rates after carotid endarterectomy have been hampered by problems with sample size and accuracy of data on smoking habits. In addition, since most studies involve analysis of multiple factors, attempts at univariate analysis may not represent the true effect of cigarette smoke alone. Our study used equal numbers in each cohort group and in controls to ensure uniformity of effect among all groups studied. We also analyzed the dose-response effect of cigarette smoke on the development of intimal hyperplasia using a standard animal model to allow for study of a single variable in a controlled environment. Although control animals were not restrained in a manner similar to that of smoke-exposed animals during the course of the experiment, previous work in our laboratory demonstrated no significant differences in intimal hyperplasia development between restrained and unrestrained control animals (M.M.L, unpublished data, 1994).
The animals used in this study develop lesions after endothelial denudation similar to those found in areas of human intimal hyperplasia. This model has been used extensively by our laboratory and other investigators28 29 30 31 32 33 34 35 36 37 in studies of intimal hyperplasia. Although there are differences between the rat balloon catheter injury model compared with human restenosis after carotid endarterectomy, both processes involve the development of intimal hyperplasia. This process is usually attenuated in rats after 6 weeks but continues unabated in human lesions. Our model harvests the carotid artery 4 weeks after intimal injury to obtain hyperplastic lesions during the active proliferation phase (similar to that found in humans after intimal injury). Damage to the endothelium and media is a prominent feature in this model, as it is in human arteries after carotid endarterectomy, balloon angioplasty, atherectomy, and vein grafting. These lesions consist of a thickened intima with abundant smooth muscle cells and matrix (collagen, elastin, and proteoglycans); human lesions display prolific matrix but relatively fewer smooth muscle cells.23 38 39 40 41 42 43 44 45 46 Endothelial denudation is followed by platelet adherence to the exposed thrombogenic subendothelium. Platelets then spread and release vasoactive and thrombogenic factors, as well as growth factors (platelet-derived growth factor, transforming growth factor-ß, and epidermal growth factor).47 These factors are mitogenic for smooth muscle ingrowth and matrix deposition, with resultant intimal hyperplasia formation.
We have demonstrated a statistically significant increase in the development of intimal hyperplasia in the common carotid artery after exposure to smoke from 6 or 8 cigarettes per day. Animals exposed to 3 or fewer cigarettes per day failed to demonstrate a significant increase in intimal hyperplasia development. This suggests a threshold level at which the stimulatory effect of cigarette smoke is expressed. This effect of high-dose cigarette smoke may be secondary to alterations in platelet, endothelial cell, neutrophil, or smooth muscle cell functions or a combination thereof. Many studies have demonstrated an increase in the number of platelets or their activity after exposure to cigarette smoke.48 49 50 51 52 Rangemark et al51 showed an increase in both platelet number and in platelet/vessel wall interaction with smoke exposure. These effects were not seen with exposure to nicotine alone,49 and no sex differences were noted.51 In addition to an increased ability to aggregate, smoke also affects platelet biochemistry. Smith et al53 54 demonstrated inhibition of platelet mitochondrial activity after exposure to cigarette smoke. Although smokers demonstrate chronic activation of their platelets,50 the effect is reversible.50 52
Endothelial cells are also affected by exposure to cigarette smoke and may be responsible for the threshold effect seen with high-dose exposure. Injury to the endothelium from smoking disrupts normal regulatory properties and results in abnormal endothelial cell function.55 Endothelial cell wall permeability is increased, as is the likelihood of detachment with injury.56 In addition, smokers demonstrate decreased endothelial cell DNA synthesis.57 Similar to the reversible effects of cigarette smoke on platelets, endothelial dysfunction in smokers also does not appear to be permanent.58 Although our model uses denudation of endothelium to stimulate development of intimal hyperplasia, exposure to cigarette smoke before injury may potentiate the posttraumatic reaction of platelet and neutrophil stimulation and smooth muscle cell recruitment. In some models of atherosclerosis, for instance, endothelial cell dysfunction in smokers was shown before anatomic evidence of plaque formation was seen.59
Neutrophils are responsible for the release of vasoactive and mitogenic factors after injury and are integral to the development of intimal hyperplasia after endothelial injury. Smokers demonstrate alterations in neutrophil function at both the cellular and molecular levels.49 56 60 61 62 63 64 65 Cigarette smoke increases white blood cell counts49 and increases the activation of neutrophils by the complement system.65 Chemotactic functions of neutrophils are affected by smoke exposure,62 as is the production,60 composition,56 61 63 64 and release60 of neutrophil granules. Because of the importance of neutrophils in the initial stages of intimal hyperplasia development, any alterations in function secondary to cigarette smoke would likely affect vessel restenosis after injury.
Smooth muscle cell proliferation with associated extracellular matrix deposition results in the development of the intimal hyperplasia lesions actually responsible for luminal obstruction. Although the increased smooth muscle cell proliferation found in smokers may be secondary to endothelial and neutrophil dysfunction, there is also evidence that cigarette smoke itself may be responsible.55 66 67 68 Higman et al66 demonstrated smooth muscle cell proliferation, increased vasomotor tone, and impaired endothelium-derived relaxation from endothelium-derived relaxing factor in cigarette smokers. He67 found increased smooth muscle cell proliferation and migration to the intima of arteries after smoke exposure with a concomitant increase in extracellular matrix production. Polycyclic aromatic hydrocarbons in cigarette smoke, often implicated in the development of atherogenesis, have also been shown to increase smooth muscle cell proliferation and viability.68
The primary purpose of our study was to demonstrate the clinical effect of cigarette smoke on intimal hyperplasia. We did not seek to actually isolate the particular component(s) responsible for this effect. We hypothesize that exposure to carbon monoxide may play a role in the augmentation of intimal hyperplasia development after endothelial injury. Preliminary studies in this laboratory (P.V.P. et al, unpublished data, 1994) have demonstrated dose-responsive elevations in carbon monoxide and hemoglobin in rats exposed to cigarette smoke in an identical apparatus. Further immunohistochemical analysis with the use of monoclonal antibodies is currently under way to isolate the component(s) of intimal hyperplasia affected by cigarette smoke.
We conclude that high-dose cigarette smoke accelerates development of intimal hyperplasia in the injured rat carotid artery. Because of the similar intimal hyperplasia response in human carotid arteries after endothelial damage, smoking likely represents a significant risk factor in developing carotid restenosis and stroke. This effect was not demonstrated with low-dose exposure to cigarette smoke.
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Acknowledgments |
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This study was supported in part by a grant from the Joash Foundation and the Veterans Administration merit review No. 911-040. We would like to thank Ted Henderson for performing the planimetry measurements and for his assistance with the care and preparation of animal subjects.
Received December 20, 1994; revision received March 17, 1995; accepted April 26, 1995.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Lang J, Lynch T, Karanfilian R, Hobson R. Asymptomatic carotid disease. Surg Gynecol Obstet. 1985;160:89-98. [Medline] [Order article via Infotrieve]
2. Adelman S. Economic impact: report on the National Survey of Stroke (American Heart Association monograph No. 75). Stroke. 1981;12(suppl I, pt 2):I-69-I-87.
3. European Carotid Surgery Trialists' Collaborative Group. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. Lancet. 1991;337:1235-1243. [Medline] [Order article via Infotrieve]
4. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high grade stenosis. N Engl J Med. 1991;325:445-453. [Abstract]
5.
Gelabert HA, El-Massry S, Moore WS. Carotid
endarterectomy with primary closure does not
adversely affect the rate of recurrent stenosis.
Arch Surg. 1994;129:648-654.
6. Atnip RG, Wengrovitz M, Gifford RR, Neumyer MM, Thiele BL. A rational approach to recurrent carotid stenosis. J Vasc Surg. 1990;11:511-516. [Medline] [Order article via Infotrieve]
7. Park Y, El-Bayar H, Hye R, Stabile B, Freischlag J. Safety and long-term benefit of carotid endarterectomy in the asymptomatic patient. Ann Vasc Surg. 1990;4:218-222. [Medline] [Order article via Infotrieve]
8.
Zierler R, Bandyk D, Thiele B, Strandness D.
Carotid artery stenosis following
endarterectomy. Arch Surg. 1982;117:1408-1415.
9. Salvian A, Baker J, Machleder H, Busuttil R, Barker W, Moore W. Cause and noninvasive detection of restenosis after carotid endarterectomy. Am J Surg. 1983;146:29-34. [Medline] [Order article via Infotrieve]
10. Ricotta JJ, O'Brien MS, DeWeese JA. Natural history of recurrent and residual stenosis after carotid endarterectomy: implications for postoperative surveillance and surgical management. Surgery. 1992;112:656-663. [Medline] [Order article via Infotrieve]
11.
DeGroote R, Lynett T, Jamil Z, Hobson RI.
Carotid restenosis: long-term noninvasive follow-up
after carotid endarterectomy.
Stroke. 1987;18:1031-1036.
12. Sanders E, Hooneveld H, Eikelboom B, Ludwig J, Vermenlen F, Ackerstaff R. Residual lesions and recurrent stenosis after carotid endarterectomy. J Vasc Surg. 1987;5:731-737. [Medline] [Order article via Infotrieve]
13. Healy D, Zierler R, Nicholls S, Clowes A, Primozich J, Bergelin R, Strandness DJ. Long-term follow-up and clinical outcome of carotid restenosis. J Vasc Surg. 1989;10:662-669. [Medline] [Order article via Infotrieve]
14.
Callow A. Recurrent stenosis after
carotid endarterectomy. Arch
Surg. 1982;117:1082-1085.
15. Clagett G, Rich N, McDonald P, Salander J, Youkey J, Olson D, Hutton JJ. Etiologic factors for recurrent carotid artery stenosis. Surgery. 1983;93:313-318. [Medline] [Order article via Infotrieve]
16. Thomas M, Otis S, Rush M, Zyroff J, Dilley R, Bernstein E. Recurrent carotid artery stenosis following endarterectomy. Ann Surg. 1984;200:76-79.
17. Ouriel K, Green R. Clinical and technical factors influencing recurrent carotid stenosis and occlusion after endarterectomy. J Vasc Surg. 1987;5:702-706. [Medline] [Order article via Infotrieve]
18. Reilly L, Okuhn S, Rapp J. Recurrent carotid stenosis: a consequence of local or systemic factors? The influence of unrepaired technical defects. J Vasc Surg. 1990;11:448-460. [Medline] [Order article via Infotrieve]
19. Griffith R, Standafer S. Simultaneous mainstream, sidestream smoke exposure systems, II: the rat exposure system. Toxicology. 1985;35:13-24. [Medline] [Order article via Infotrieve]
20. Griffith R, Hancock R. Simultaneous mainstream, sidestream smoke exposure systems, I: equipment and procedures. Toxicology. 1985;34:123-138. [Medline] [Order article via Infotrieve]
21. Stoney R, String S. Recurrent carotid stenosis. Surgery. 1976;80:705-710. [Medline] [Order article via Infotrieve]
22. Imparato A, Bracco A, Kim G, Zeff R. Intimal and neointimal fibrous proliferation causing failure of arterial reconstructions. Surgery. 1972;72:1007-1017. [Medline] [Order article via Infotrieve]
23. Szilagyi D, Elliot J, Hageman J, Smith R, Dall'olmo C. Biologic fate of autogenous vein implants as arterial substitutes: clinical, angiographic, and histopathologic observations in femoropopliteal operations for atherosclerosis. Ann Surg. 1973;178:232-245. [Medline] [Order article via Infotrieve]
24. Baker W, Hayes A, Mahler D, Littooy F. Durability of carotid endarterectomy. Surgery. 1983;94:112-115. [Medline] [Order article via Infotrieve]
25. Keagy B, Edrington R, Poole M, Johnson G. Incidence of recurrent or residual stenosis after carotid endarterectomy. Am J Surg. 1985;149:722-725. [Medline] [Order article via Infotrieve]
26. Barnes R, Nix M, Nichols B, Wingo J. Recurrent versus residual carotid stenosis: incidence detected by Doppler ultrasound. Ann Surg. 1986;203:652-660. [Medline] [Order article via Infotrieve]
27. Mattos M, Shamma A, Rossi N, Meng R, Godersky J, Loftus C, Corson J. Is duplex follow up cost effective in the first year after carotid endarterectomy? Am J Surg. 1988;156:91-95. [Medline] [Order article via Infotrieve]
28.
Clowes A, Schwartz S. Significance of quiescent
smooth muscle migration in the injured rat carotid artery.
Circ Res. 1985;56:139-145.
29. Clowes A, Reidy M, Clowes M. Mechanisms of stenosis after arterial injury. Lab Invest. 1983;49:208-215. [Medline] [Order article via Infotrieve]
30. Clowes A, Rosenberg R, Clowes M. Regulation of arterial smooth muscle cell proliferation by heparin in vivo. Surg Forum. 1983;34:357-360.
31. Clowes A, Clowes M, Fingerle J, Reidy M. Kinetics of cellular proliferation after arterial injury: role of acute distension in the induction of smooth muscle proliferation. Lab Invest. 1989;60:360-364. [Medline] [Order article via Infotrieve]
32.
Clowes A, Clowes M, Kocher O, Ropraz P, Chaponnier C,
Gabbiani G. Arterial smooth muscle cells in vivo:
relationship between actin isoform expression and mitogenesis and their
modulation by heparin. J Cell Biol. 1988;107:1939-1945.
33.
Cerek B, Fishbein M, Forrester J, Helfant R, Fagin J.
Induction of vascular insulin-like growth factor-I messenger RNA
in rat aorta after balloon denudation. Circ
Res. 1990;66:1755-1760.
34.
Daemen M, Lombardi D, Bosman F, Schwartz S.
Angiotensin II induces smooth muscle cell
proliferation in the normal and injured rat arterial
wall. Circ Res. 1991;68:450-456.
35. Ferns G, Reidy M, Ross R. Balloon catheter de-endothelialization of the nude rat carotid: response to injury in the absence of functional T lymphocytes. Am J Pathol. 1991;138:1045-1057. [Abstract]
36.
Ferns G, Raines E, Sprugel K, Motani A, Reidy M, Ross
R. Inhibition of neointimal smooth muscle
accumulation after angioplasty by an antibody to PDGF.
Science. 1991;253:1129-1132.
37. Jawien A, Bowen-Pope D, Clowes A. Platelet-derived growth factor promotes smooth muscle cell migration and intimal thickening in a rat model of balloon angioplasty. J Clin Invest. 1992;89:507-511.
38.
Liu M, Roubin G, King S. Restenosis
after coronary angioplasty: potential biologic determinants and
role of intimal hyperplasia. Circulation. 1989;79:1374-1387.
39. Claggett C, Robinowitz M, Youkey J, Fisher D, Fry R, Myers S, Lee E, Collins G, Virami R. Morphogenesis and clinicopathologic characteristics of recurrent carotid disease. J Vasc Surg. 1986;3:10-23. [Medline] [Order article via Infotrieve]
40. Sterpetti A, Schultz R, Feldhaus R, Hunter W, Bailey RJ, Hacker K, Davenport K, Richardson M, Farina C. Natural history of recurrent carotid artery disease. Surg Gynecol Obstet. 1989;168:217-223. [Medline] [Order article via Infotrieve]
41. Klein L, Rosenblum J. Restenosis after successful percutaneous transluminal coronary angioplasty. Prog Cardiovasc Dis. 1990;:365-382.
42. Pompa J, Topol E. Factors influencing restenosis after coronary angioplasty. Am J Med. 1990;88:16N-24N. [Medline] [Order article via Infotrieve]
43. Giraldo A, Esposo O, Meis J. Intimal hyperplasia as a cause of restenosis after percutaneous transluminal coronary angioplasty. Arch Pathol Lab Med. 1985;109:173-175. [Medline] [Order article via Infotrieve]
44.
Safian R, Gelbfish J, Erny R, Schnitt S, Schmidt D,
Baim D. Coronary atherectomy: clinical, angiographic,
and histological findings and observations.
Circulation. 1990;82:69-79.
45. Campeau L. Late changes in saphenous vein coronary artery bypass grafts and their implications in clinical practice. Can J Cardiol. 1987;3(suppl A):23A-29A.
46. Unni K, Kottke B, Titus J, Frye R, Wallace R, Brown A. Pathologic changes in aortocoronary saphenous vein grafts. Am J Cardiol. 1974;34:526-532. [Medline] [Order article via Infotrieve]
47.
Kohler TR, Jawien A. Flow affects development of
intimal hyperplasia after arterial injury in rats.
Arterioscler Thromb. 1992;12:963-971.
48. Terres W, Becker P, Rosenberg A. Changes in cardiovascular risk profile during the cessation of smoking. Am J Med. 1994;97:242-249. [Medline] [Order article via Infotrieve]
49. Benowitz N, Fitzgerald G, Wilson M, Zhang Q. Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking. J Am Coll Cardiol. 1993;22:1159-1167. [Abstract]
50.
Rangemark C, Ciabattoni G, Wennmalm A. Excretion
of thromboxane metabolites in healthy women after cessation of
smoking. Arterioscler Thromb. 1993;13:777-782.
51.
Rangemark C, Benthin G, Ganstrom E, Persson L, Winell
S, Wennmalm A. Tobacco use and urinary excretion of
thromboxane A2 and prostacyclin metabolites in women stratified
by age. Circulation. 1992;86:1495-1500.
52. Chiang V, Castleden W, Leahy M. Detection of reversible platelet aggregates in the blood of smokers and ex-smokers with peripheral vascular disease. Med J Aust. 1992;156:601-603. [Medline] [Order article via Infotrieve]
53. Smith P, Cooper J, Govan G, Harding A, Schapira A. Platelet mitochondrial function in Leber's hereditary optic neuropathy. J Neurol Sci. 1994;122:80-83. [Medline] [Order article via Infotrieve]
54. Smith P, Cooper J, Govan G, Harding A, Schapira A. Smoking and mitochondrial function: a model for environmental toxins. Q J Med. 1993;86:657-660.
55. Nabel E. Biology of the impaired endothelium. Am J Cardiol. 1991;68:6C-8C. [Medline] [Order article via Infotrieve]
56. MacNee W, Bridgeman M, Marsden M, Drost E, Lannan S, Selby C, Donaldson K. The effects of N-acetylcysteine and glutathione on smoke-induced changes in lung phagocytes and epithelial cells. Am J Med. 1991;91:60S-66S. [Medline] [Order article via Infotrieve]
57. Falke P, Mattiasson I, Stavenow L. Effects of platelets from men with risk factors for atherosclerosis on endothelial cell proliferation and prostacyclin production in vitro. Scand J Clin Lab Invest. 1993;53:297-303. [Medline] [Order article via Infotrieve]
58. Jacobs M, Lenders J, Kapma J, Smits P, Thien T. Effect of chronic smoking on endothelium-dependent vascular relaxation in humans. Clin Sci. 1993;85:51-55. [Medline] [Order article via Infotrieve]
59. Celermajer D, Sorensen K, Gooch V, Spiegelhalter D, Miller O, Sullivan I, Lloyd J, Deanfield J. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111-1115. [Medline] [Order article via Infotrieve]
60. Jensen E, Pedersen B, Schmidt E, Venge P, Dahl R. Serum eosinophilic cationic protein and lactoferrin related to smoking history and lung function. Eur Respir J. 1994;7:927-933. [Abstract]
61. Gadek J. Adverse effects of neutrophils on the lung. Am J Med. 1992;92:27S-31S. [Medline] [Order article via Infotrieve]
62. Ciaccia A, Papi A, Tschirky B, Fregan B. Protection of erdosteine on smoke-induced peripheral neutrophil dysfunction both in healthy and in bronchitic smokers. Fund Clin Pharmacol. 1992;6:375-382. [Medline] [Order article via Infotrieve]
63. Venge P, Rak S, Steinholtz L, Hakannson L, Lindblad G. Neutrophil function in chronic bronchitis. Eur Respir J. 1991;4:536-543. [Abstract]
64. Moszczynski P, Slowinski S, Moszczynski PJ. Effect of smoking on enzyme composition and neutrophil function. Pneumol Alergol Pol. 1991;59:17-21.
65. Robbins R, Gossman G, Nelson K, Koyama S, Thompson A, Rennard S. Inactivation of chemotactic factor inactivator by cigarette smoke: a potential mechanism of modulating neutrophil recruitment to the lung. Am Rev Respir Dis. 1990;142:763-768. [Medline] [Order article via Infotrieve]
66. Higman D, Greenhalgh R, Powell J. Smoking impairs endothelium-dependent relaxation of saphenous vein. Br J Surg. 1993;80:1242-1245. [Medline] [Order article via Infotrieve]
67. He J. Qualitative and quantitative observations of smoking-induced morphologic changes in muscular pulmonary arteries. Chin J Tubercol Resp Dis. 1992;15:92-94.
68. Pessah-Rasmussen H, Stavenow L, Xu C, Berglund A. Increased smooth muscle cell proliferation by dimethylbenzanthracene is correlated to variations in activity of ornithine decarboxylase but not arylhydrocarbonhydroxylase. Artery. 1991;18:240-255. [Medline] [Order article via Infotrieve]
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 |
|
  T. Anazawa, P. C. Dimayuga, H. Li, S. Tani, J. Bradfield, K.-Y. Chyu, S. Kaul, P. K. Shah, and B. Cercek Effect of Exposure to Cigarette Smoke on Carotid Artery Intimal Thickening: The Role of Inducible NO Synthase Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1652 - 1658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Conklin, W. Zhao, D.-S. Zhong, and C. Chen Nicotine and Cotinine Up-Regulate Vascular Endothelial Growth Factor Expression in Endothelial Cells Am. J. Pathol., February 1, 2002; 160(2): 413 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Liapis, J. D. Kakisis, V. G. Papavassiliou, K. M. Koumakis, and J. G. Gogas Risk Factors Associated with Recurrent Carotid Artery Stenosis Vascular and Endovascular Surgery, November 1, 1999; 33(6): 697 - 704. [Abstract] [PDF]
|
|
|
|
|
|
A. Mezzetti, M. D. Guglielmi, S. D. Pierdomenico, F. Costantini, F. Cipollone, D. De Cesare, T. Bucciarelli, S. Ucchino, F. Chiarelli, F. Cuccurullo, et al. Increased Systemic Oxidative Stress After Elective Endarterectomy : Relation to Vascular Healing and Remodeling Arterioscler. Thromb. Vasc. Biol., November 1, 1999; 19(11): 2659 - 2665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I Aldoori and S. H Rahman Smoking and stroke: a causative role BMJ, October 10, 1998; 317(7164): 962 - 763. [Full Text]
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